Oxidant-free Rh(III)-catalyzed direct C-H olefination of arenes with allyl acetates

Article abstract of DOI:10.1021/ol4015442

Rh(III)-catalyzed direct olefination of arenes with allyl acetate via C-H bond activation is described using N,N-disubstituted aminocarbonyl as the directing group. The catalyst undergoes a redox neutral process, and high to excellent yields of trans-products are obtained. This protocol exhibits a wide spectrum of functionality compatibility because of the simple reaction conditions employed and provides a highly effective synthetic method in the realm of C-H olefination.

Full text of DOI:10.1021/ol4015442

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Oxidant-Free Rh(III)-Catalyzed Direct CꢀH
Olefination of Arenes with Allyl Acetates
Chao Feng,†,‡ Daming Feng,†,‡ and Teck-Peng Loh*,§
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical
Sciences, Nanyang Technological University, Singapore 637371, Singapore, and Department of
Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China
teckpeng@ntu.edu.sg
Received June 1, 2013
ABSTRACT
Rh(III)-catalyzed direct olefination of arenes with allyl acetate via CꢀH bond activation is described using N,N-disubstituted aminocarbonyl as the directing
group. The catalyst undergoes a redox neutral process, and high to excellent yields of trans-products are obtained. This protocol exhibits a wide spectrum of
functionality compatibility because of the simple reaction conditions employed and provides a highly effective synthetic method in the realm of CꢀH olefination.
Over the past decades, transition-metal-catalyzed oxi-
dative olefination of arenes through direct CꢀH bond
activation has been demonstrated to be an effective and
efficient synthetic protocol for introducing an alkene moiety
(Scheme 1, eq 1).1 A diversity of arene CꢀH olefinations
catalyzed by different transition metals has been reported.2
The use of ortho-directing groups (DG), such as imino,3
2- imidazolyl,4 carbonyl,5 amido,6 hydroxyl,7 and 2-sub-
stituted pyridyl8 have been commonly adopted to improve
the regioselectivity as well as reaction efficiency of the
reaction. Theoretically, an oxidant is needed to regenerate
the active catalyst. However, the forced use of external
oxidants provides relatively harsh reaction conditions and
produces stoichiometric amounts of related heavy metal
wastes.
In the arena of CꢀH activation, one emerging strategy
is the use of entities which act as both DG and internal
oxidants (DGOx) at the same time (eq 2). Some traditional
directing groups, N-oxides,9 oxime ester, and N-methoxy-
amides,10 were found to play a dual role in such an
olefination process. The Pd-catalyzed olefination of quino-
line-N-oxides reported by Cui and Wu11 gives the idea that
cleavage of NꢀO bonds can act as both an inducing
platform and an oxidant in the olefination reaction.
Although the reaction required a high reaction temperature,
(2) For Pd-catalyzed CꢀH olefination, see: (a) Miura, M.; Tsuda, T.;
Satoh, T.; Pivsa-Art, S.; Nomura, M. J. Org. Chem. 1998, 63, 5211. (b)
Yokota, T.; Tani, M.; Sakaguchi, S.; Ishii, Y. J. Am. Chem. Soc. 2003, 125,
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Chem., Int. Ed. 2003, 42, 3512. (d) Zaitsev, V. G.; Daugulis, O. J. Am.
Chem. Soc. 2005, 127, 4156. (e) Beck, E. M.; Grimster, N. P.; Hatley, R.;
Gaunt, M. J. J. Am. Chem. Soc. 2006, 128, 2528. (f) Cai, G.; Fu, Y.; Li, Y.;
Wan, X.;Shi, Z.J. Am. Chem. Soc. 2007, 129, 7666. (g)Cho, S. H.;Hwang,
S. J.; Chang, S. J. Am. Chem. Soc. 2008, 130, 9254. (h) Houlden, C. E.;
Bailey, C. D.; Ford, J. G.; Gagne, M. R.; Lloyd-Jones, G. C.; Booker-
Milburn, K. I. J. Am. Chem. Soc. 2008, 130, 10066. (i) Li, J.-J.; Mei, T.-S.;
Yu, J.-Q. Angew. Chem., Int. Ed. 2008, 47, 6452. (j) Garcia-Rubia, A.;
Arrayas, R. G.; Carretero, J. C. Angew. Chem., Int. Ed. 2009, 48, 6511. (k)
Lam, J. K.; Wang, D.-H.; Yu, J.-Q. J. Am. Chem. Soc. 2010, 132, 460. (l)
Wang, D.-H.; Engle, K. M.; Shi, B.-F.; Yu, J.-Q. Science 2010, 327, 315.
(m) Wasa, M.; Engle, K. M.; Yu, J.-Q. J. Am. Chem. Soc. 2010, 132, 3680.
(n) Lu, Y.; Wang, D.-H.; Engle, K. M.; Yu, J.-Q. J. Am. Chem. Soc. 2010,
132, 5916. (o) Stowers, K. J.; Fortner, K. C.; Sanford, M. S. J. Am. Chem.
Soc. 2011, 133, 6541. For Rh-catalyzed CꢀH olefination, see: (p) Stuart,
D. R.;Bertrand-Laperle, M.;Burgess, K. M. N.; Fagnou, K.J. Am. Chem.
Soc. 2008, 130, 16474. (q)Guimond, N.;Gorelsky, S. I.;Fagnou, K.J. Am.
Chem. Soc. 2011, 133, 6449. (r)Guimond, N.;Gouliaras, C.; Fagnou, K. J.
Am. Chem. Soc. 2010, 132, 6908. (s) Sturat, D. R.; Alsabeh, P.; Kuhn, M.;
Fagnou, K. J. Am. Chem. Soc. 2010, 132, 18326. (t) Li, Y.; Li, B.-J.; Wang,
W.-H.; Huang, W.-P.; Zhang, X.-S.; Chen, K.; Shi, Z.-F. Angew. Chem.,
Int. Ed. 2011, 50, 2115. (u) Tsai, A. S.; Tauchert, M. E.; Bergman, R. G.;
Ellman, J. A. J. Am. Chem. Soc. 2011, 133, 1248. (v) Guimond, N.;
Fagnou, K. J. Am. Chem. Soc. 2009, 131, 12050. (w) Patureau, F. W.;
Besset, T.; Kuhl, N.; Glorius, F. J. Am. Chem. Soc. 2011, 133, 2154. (x)
Rakshit, S.; Patureau, F. W.; Glorius, F. J. Am. Chem. Soc. 2010, 132,
9585. (y) Su, Y.; Zhao, M.; Han, K.; Song, G.; Li, X. Org. Lett. 2010, 12,
5462. (z) Song, G.; Chen, D.; Pan, C.-L.; Crabtree, R. H.; Li, X. J. Org.
Chem. 2010, 75, 7487. (aa) Wang, F.; Song, G.; Du, Z.; Li, X. J. Org.
Chem. 2011, 76, 2926. (bb) Too, P. C.; Wang, Y.-F.; Chiba, S. Org. Lett.
2010, 12, 5688. (cc) For Ru-catalyzed CꢀH olefination, see: Ueyama, T.;
Mochida, S.; Fukutani, T.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett.
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† These authors contributed equally.
‡ Nanyang Technological University.
§ University of Science and Technology of China.
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Fujiwara, Y. Science 2000, 287, 1992. (b) Jia, C.; Kitamura, T.;
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r
10.1021/ol4015442
XXXX American Chemical Society

olefination reaction of N,N-disubstituted benzamide with
allyl acetate without any external oxidants.16
Scheme 1. Transition-Metal-Catalyzed Oxidative Olefination
Table 1. Optimization of Reaction Conditionsa
it proposed the possibility of improving the atom efficiency
and decreasing toxic waste formation. Recently, Fagnou
et al. reported the Rh(III)-catalyzed isoquinoline construc-
tion using the NꢀO bond of N-methoxylbenzamide as an
inner oxidant.12 Following this idea, Glorius et al. devel-
oped the Rh(III)-catalyzed olefinations, which proceed
under mild reaction condition and tolerate a broad range
of functionalities.13 Meanwhile, an interesting allylation of
arenes was disclosed by Ellman, using allyl acetate as the
coupling partner.14 Although a substoichiometric amount
ofCu(OAc)2 is still needed to maintain the yield, this finding
did invoke the possibility of oxidant-free CꢀH olefination.
With our continuing interest in Rh-catalysis15 and to dis-
cover a new protocol in the realm of CꢀH olefination, we
would like to report, herein, the Rh(III)-catalyzed CꢀH
entry
catalyst
additive
solvent
yieldb (%)
1
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
ꢀ
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgOAc
ꢀ
DME
62
2
dioxane
DCE
58
3
92
4
THF
74
5
t-AmOH
acetone
MeCN
DCE
53
6
80
7
NR
NR
NR
NR
NRc
8
9
DME
10
11
AgSbF6
AgSbF6
DME
[Cp*RhCl2]2
DME
a Unless otherwise noted the reactions were carried out at 110 °C
using 1a (0.2 mmol), 2a (0.24 mmol), catalyst (0.0025 mmol), and
additive (0.01 mmol) in solvent (1 mL) stirred for 16 h. b Isolated yields.
c K2CO3 (0.2 mmol) was added. DCE = 1,2-dichloroethane, DME =
1,2-dimethoxylethane.
(3) (a) Oi, S.; Ogino, Y.; Fukita, S.; Inoue, Y. Org. Lett. 2002, 4, 1783.
(b) Ackermann, L. Org. Lett. 2005, 7, 2229.
(4) Oi, S.; Aizawa, E.; Ogino, Y.; Inoue, Y. J. Org. Chem. 2005, 70,
3113.
At the outset of our studies, the reaction conditions were
optimized using N,N-dimethylbenzamide (1a) and allyl
acetate (2a) as the model substrates. After extensive trials,
we were pleased to find that 62% yield of the desired
olefination product could be obtained. Guided by the
dramatic solvent effect observed in our previous work, a
series of solvents were subsequently examined and 1,2-
dichloroethane proved to be the optimal choice (Table 1,
entries 1ꢀ7).15 Much to our surprise, when AgOAc
was added instead of AgSbF6, no reaction occurred,
which indicates the vital importance of a cationic rhodium
catalyst in the catalytic cycle (Table 1, entry 8). Not
surprisingly, the reaction did not proceed in the absence
of either the Rh(III) catalyst or silver additive (Table 1,
entries 9, 10). In addition, when a stoichiometric amount
of K2CO3 was added, the reaction was totally suppressed
(Table 1, entry 11).
With the optimized reaction condition in hand, we
turned our attention to the exploration of the reaction
scope of various N,N-disubstituted benzamide derivatives
with allyl acetate (2a) as the model coupling partner. Both
electron-donating and -withdrawing functional groups at
the para-position of N,N-dimethyl amide group were well
adapted in this reaction, and corresponding olefination
products were obtained in high yields (Scheme 2, 3bꢀ3l).
Notably, methoxy (3c), TMS (3d), trifluoromethyl (3e),
bromo (3i), acetal (3j), and ester (3k), which are valuable
functional groups amenable for further derivatization,
were all well tolerated. 2-Naphthamide was also a suitable
substrate, giving the C3-olefination product in 82% yield
(Scheme 2, 3m). As HOAc is formed in this catalytic cycle,
(5) (a) Satoh, T.; Kametani, Y.; Terao, Y.; Miura, M.; Nomura, M.
Tetrahedron Lett. 1999, 40, 5345. (b) Kawatsura, M.; Hartwig, J. J. Am.
Chem. Soc. 1999, 121, 1473. (c) Kakiuchi, F.; Kan, S.; Igi, K.; Chatani,
N.; Murai, S. J. Am. Chem. Soc. 2003, 125, 1698. (d) Kakiuchi, F.;
Matsuura, Y.; Kan, S.; Chatani, N. J. Am. Chem. Soc. 2005, 127, 5936.
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Chem., Int. Ed. Engl. 1997, 36, 1740. (b) Bedford, R. B.; Coles, S. J.;
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2005, 127, 18020. (b) Leclerc, J. P.; Fagnou, K. Angew. Chem., Int. Ed.
2006, 45, 7781. (c) Campeau, L. C.; Bertrand-Laperle, M.; Leclerc, J. P.;
Villemure, E.; Gorelsky, S.; Fagnou, K. J. Am. Chem. Soc. 2008, 130,
3266. (d) Campeau, L. C.; Schipper, D. J.; Fagnou, K. J. Am. Chem. Soc.
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Soc. 2008, 130, 7190. (b) Wasa, M.; Yu, J.-Q. J. Am. Chem. Soc. 2008,
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2009, 131, 13888.
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2010, 132, 6908.
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(b) Zhang, J.; Loh, T. P. Chem. Commun. 2012, 48, 11232.
(16) While preparing our manuscript, Glorius et al. reported a similar
protocol for Rh(III)-catalyzed direct CꢀH allylation of arenes using
€
allyl carbonates: Wang, H.; Schroder, N.; Glorius, F. Angew. Chem., Int.
Ed. 2013, 52, 5386.
B
Org. Lett., Vol. XX, No. XX, XXXX

the weak acidity of the reaction media would lead to
decomposition of the dioxole group, which gave a moder-
ate yield of 64% (Scheme 2, 3n). With regard to a meta-
methyl substituted substrate, the reaction selectively hap-
penedat a stericallymore accessible site, thusdeliveringthe
desired product in high yield (Scheme 2, 3o). However, for
the meta-Cl substituted analogue, the reaction tended to
afford a mixture of two regioisomers (Scheme 2, 3p, 3p0).
When an ortho-methyl substituted N,N-dimethylbenza-
mide substrate was engaged in such an olefination reac-
tion, a mixture of the allylation product and alkenylation
products was obtained with an isomeric ratio of 1:1
(Scheme 3).
Table 2. Scope of Allyl Acetate Derivativesa
Scheme 2. Scope of N,N-Dimethylbenzamide Derivativesa,b
a Unless otherwise noted the reactions were carried out at 110 °C
using 1a (0.2 mmol), 2 (0.24 mmol), [Cp*RhCl2]2 (0.0025 mmol), and
AgSbF6 (0.01 mmol) in DCE (1 mL) stirred for 16 h. b Isolated and two-
step total yield. c [Cp*RhCl2]2 (0.005 mmol) and AgSbF6 (0.02 mmol)
were used. d Reaction temperature is 140 °C.
In order to have a better understanding of the protocol,
we proceeded to explore the scope of allyl electrophilic
partners. While linear allyl acetates, such as cinnamyl
acetate, were unreactive, the branched isomer 2-phenylallyl
acetate showed good reactivity to afford the trans product
(Scheme 4). The low yield was attributed to the steric
hindrance of the bulky phenyl group. Meanwhile, high
yields were obtained with the 1-substituted allyl acetates, of
which the products were observed to be mixtures of isomers
(Table 2). In order to simplify the characterization of the
products, further hydrogenation was adopted. The reac-
tion proceeded readily with complete γ-selectivity, and no
terminal alkene product was formed. Compared to aliphatic
substituted allyl acetates, those with aromatic substituents
afford the desired product in relatively higher yield.
a Unless otherwise noted the reactions were carried out at 110 °C
using 1a (0.2 mmol), 2a (0.24 mmol), [Cp*RhCl2]2 (0.0025 mmol),
AgSbF6 (0.01 mmol) in DCE (1 mL) stirred for 16 h. b Isolated yields.
c Catalyst (0.005 mmol) was used. DCE = 1,2-dichloroethane.
Scheme 3. CꢀH Olefination of ortho-Methyl Substituted
N,N-Dimethylbenzamide with 2aa
To obtain more detailed information about the mechan-
ism of the present olefination reaction, the following
experiments were conducted asshown in Scheme 5. Signifi-
cant isotope effects were observed in either the intramole-
cular or intermolecular studies (Scheme 5), thus indicating
a The reactions were carried out at 110 °C using 1q (0.2 mmol), 2a
(0.24 mmol), [Cp*RhCl2]2 (0.005 mmol), and AgSbF6 (0.02 mmol) in
DCE (1 mL) stirred for 16 h.
Org. Lett., Vol. XX, No. XX, XXXX
C

Scheme 4. Alkene Counterpart Comparison: Terminal vs
Internal
Scheme 6. Plausible Catalytic Mechanism
Scheme 5. Kinetic Isotope Effects
product IV and regenerate the active Rh(III) catalyst. The
final product is obtained after the migratory isomerization
of the double bond, which may due to the effect of trace
[RhꢀH] complex. Due to the conformational restriction,
the β-hydride elimination with the benzylic H-atom would
be prevented by the coordination of the directing group.
Duringthewholecatalyticcycle, theRh(III) catalystunder-
goes a redox neutral process, which indicates an oxidant-
free strategy with the acetate anion as a leaving group.
In conclusion, we have reported a novel cationic Rh(III)-
catalyzed olefination of N,N-disubstituted benzamides
with allyl acetate derivatives, which delivers trans-products
in high to excellent yields without the need for an external
oxidant. The ambient condition and high efficiency of this
reaction shows tolerance of a range of functionalities.
Acknowledgment. We gratefully acknowledge the Na-
nyang Technological University and Singapore Ministry
of Education Academic Research Fund (MOE2011-T2-1-
013) for the funding of this research.
the rationality of CꢀH bond cleavage being the rate-
determining step. In combination with the high reactivity of
highly electron-deficient substrates, a concerted-metalation-
deprotonation is most likely the plausible mechanistic
pathway.
On the basis of our experimental results, a plausible
mechanism is proposed in Scheme 6. Precomplexation of
the amide substrate with an active Rh(III) catalyst would
trigger ortho CꢀH bond activation to form the metalla-
cycle via a concerted-metalation-deprotonation pathway
to deliver the intermediate I. After migratory insertion by
the incoming alkene, a seven-membered Rh(III) species II
is formed with carbonate oxygen chelating to the metal.
Then β-acetate elimination17 would happen to give the
Supporting Information Available. Additional experi-
mental procedures and full spectroscopy data for all the
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
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The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX